This project seeks to investigate comparative efficacy of monoamine oxidase inhibitors in neurotic depression; existence of patient subtypes; differential response in such subtypes; pharmacological factors affecting response. A double-blind clinical trial is being carried out in outpatients and day hospital patients showing neurotic depression or mixed anxiety depression of mild to moderate severity. After an initial week on placebo patients are assigned randomly to phenelzine, amitriptyline or placebo and treated for six weeks. A variety of symptom rating scales are employed as outcome measures, supplemented by social and psychiatric history predictors at initial rating. Typological and regressional methods are used to develop predictors. Platelet MAO inhibition and tricyclic levels are measured. Genetic polymorphism with respect to fast or slow acetylation is determined. Pretreatment and its relation to response, diagnosis, and degree of MAO inhibition will be examined. The study is at present in the data collection phase. Analysis of a pilot sample treated openly with phenelzine has demonstrated significant clinical predictors of response.